The present invention is related to novel compounds which are 2-heterocyclic 5-hydroxy-1,3-pyrimidines and pharmaceutically acceptable acid addition or base salts thereof, pharmaceutical compositions and methods of use therefor. Particularly the invention is related to 2-thiazole, 2-oxazole, or 2-imidazole-5-hydroxy-1,3-pyrimidines. The invention compounds have activity as inhibitors of 5-lipoxygenase and/or cyclooxygenase providing treatment of conditions advantageously affected by such inhibition including, for example, rheumatoid arthritis, osteoarthritis, other inflammatory conditions, pain, fever, psoriasis, allergic diseases, asthma, inflammatory bowel disease, GI ulcers, cardiovascular conditions including ischemic heart disease and atherosclerosis, and ischemia-induced cell damage, particularly brain damage caused by stroke. They can also be used topically for treating acne, sunburn, psoriasis, and eczema. Also included are leukotriene mediated pulmonary, gastrointestinal, inflammatory, dermatological, and cardiovascular conditions. The disclosed compounds also have potential utility as antioxidants and as inhibitors of LDL into macrophages. However, overall the preferable use is to treat inflammatory conditions. Thus, the present invention is also a pharmaceutical composition or method of manufacturing a pharmaceutical composition for the use of treating the noted conditions.
3,5-Di-tertiary butyl 4-hydroxybenzene, substituted by thiazoles, oxazoles, and imidazoles are known to provide antiinflammatory activity, U.S. Pat. No. 4,636,516. 2-Substituted-5-hydroxy-1,3-pyrimidines as antiinflammatory agents are also described as copending U.S. application Ser. Nos. 07/648,115 of Jan. 31, 1991, and 07/756,400 of Sep. 9, 1991, respectively.